Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18333-8. doi: 10.1073/pnas.1420285111. Epub 2014 Dec 8.

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training.

Author information

Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy;
Department of Cognitive Neuroscience, Radboud University Medical Centre, 6501 HB Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 EZ Nijmegen, The Netherlands;
Department of Sciences, University Roma Tre, 00146 Rome, Italy;
Department of Anaesthesiology, Ludwig Maximilians University, 81377 Munich, Germany;
Department of Experimental and Clinical Medicine, University of Foggia, 71122 Foggia, Italy; and.
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy;


Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation.


anandamide; cannabinoid receptors; emotional arousal; endocannabinoids; inhibitory avoidance

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center